Background

Although elevated body mass index (BMI) is a risk factor for cardiac disease, patients with elevated BMI have better survival in the context of severe illness, a phenomenon termed the "obesity paradox."

Hypothesis

Higher BMI is associated with lower mortality in sudden cardiac arrest (SCA) survivors.

Methods

Data were collected on 1433 post-SCA patients, discharged alive from the hospitals of the University of Pittsburgh Medical Center between 2002 and 2012. Of those, 1298 patients with documented BMI during the index hospitalization and follow-up data constituted the study cohort.

Results

In the overall cohort, 30 patients were underweight (BMI <18.5 kg/m² ), 312 had normal weight (BMI 18.5-24.9 kg/m² ), 417 were overweight (BMI 25.0-29.9 kg/m² ), and 539 were obese (BMI ≥30 kg/m² ). As expected, the prevalence of coronary artery disease, myocardial infarction, diabetes mellitus, and hypertension increased significantly with increasing BMI. Over a median follow-up of 3.6 years, 602 (46%) patients died. Despite higher prevalence of cardiovascular comorbidities in more obese patients, a higher BMI was associated with lower all-cause mortality on univariate analysis (hazard ratio: 0.86 per increase by 1 BMI category, 95% confidence interval: 0.78-0.94, P = 0.002) and multivariate analysis after adjusting for unbalanced baseline comorbidities (hazard ratio: 0.86 per increase by 1 BMI category, 95% confidence interval: 0.77-0.96, P = 0.009).

Conclusions

Higher BMI is associated with lower all-cause mortality in survivors of SCA, suggesting that the obesity paradox applies to the post-arrest population. Further investigation into its mechanisms may inform the management of post-SCA patients.

Retinal ganglion cells (RGCs) relay visual information from the eye to the brain. RGCs are the first cell type generated during retinal neurogenesis. Loss of function of the transcription factor Atoh7, expressed in multipotent early neurogenic retinal progenitors leads to a selective and essentially complete loss of RGCs. Therefore, Atoh7 is considered essential for conferring competence on progenitors to generate RGCs. Despite the importance of Atoh7 in RGC specification, we find that inhibiting apoptosis in Atoh7-deficient mice by loss of function of Bax only modestly reduces RGC numbers. Single-cell RNA sequencing of Atoh7;Bax-deficient retinas shows that RGC differentiation is delayed but that the gene expression profile of RGC precursors is grossly normal. Atoh7;Bax-deficient RGCs eventually mature, fire action potentials, and incorporate into retinal circuitry but exhibit severe axonal guidance defects. This study reveals an essential role for Atoh7 in RGC survival and demonstrates Atoh7-dependent and Atoh7-independent mechanisms for RGC specification.